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PubMedDate not supplied

A review of the treatment and survival rates of 138 patients with glioblastoma multiforme.

This article reviews the cases of 138 patients at the Charleston Area Medical Center who were treated for glioblastoma multiforme (astrocytoma Grade IV) between 1966-1987. Data was obtained from the hospital's tumor registry, inpatient/outpatient records, pathology reports, as well as radiotherapy records. The median survival rate for all patients was 7 months (range 1-36 months). The median survival of the patients who underwent complete resection and received radiotherapy was 12 months, while the median survival rate was four months for patients who had complete resection but did not undergo radiotherapy. In addition, the median survival of the patients who underwent incomplete resection with radiotherapy was 10 months compared to a survival rate of 3 months of those who did not undergo radiotherapy after incomplete resection. Radiotherapy was the most significant predictor of survival with age being the major factor. Despite the clinical advancements made in the past 10-15 years, no impact has yet been achieved on the natural history of glioblastoma multiforme.

Adult↗
PubMed2004

Prognostic significance of seizure in patients with glioblastoma multiforme.

BACKGROUND: Several prognostic factors have been described but there are few studies evaluating the prognostic importance of seizure in patients with glioblastoma multiforme (GBM). AIMS: To evaluate the prognostic importance of seizure at the time of the diagnosis of glioblastoma multiforme (GBM) and compare it with other known prognostic factors. SETTINGS AND DESIGN: Between January 1994 and December 2000, 81 patients underwent irradiation for intracranial GBM at our institution. The criteria for inclusion in this study were biopsy-proven GBM, being treated for primary disease. Seventy-six patients were retrospectively evaluated and the remaining five patients could not be enrolled due to lack of details. MATERIAL AND METHODS: The prognostic importance of age, sex, performance status, a history of seizure at diagnosis, extent of surgery, radiotherapy field and dose were studied. STATISTICAL ANALYSIS: The Kaplan-Meier method, the Log rank test, the Cox proportional hazard model and the Mann-Whitney U test were used for statistical analysis. RESULTS: Survival at first and second years was 19.74% and 4.81%, respectively. Univariate analysis revealed age, performance status, history of seizure, and radiotherapy dose as significant prognostic factors and with multivariate analysis age, history of seizure and radiotherapy dose were positive prognostic factors. CONCLUSION: This study concluded that in GBM, history of seizure prior to diagnosis of GBM was a positive prognostic factor.

Adult↗
PubMed1998

Sensitization of rat glioblastoma multiforme to cisplatin in vivo following restoration of wild-type p53 function.

OBJECT: To study the combined potential of wild-type p53 gene transfer and administration of cisplatin for the treatment of glioblastoma multiforme, the authors used the 9L rat glioblastoma cell line, which expresses a mutant p53. METHODS: Stable expression of wild-type p53 in 9L cells was achieved by transfection of the cells with a wild-type p53-expressing plasmid (pCEP4p53). The resultant cell line, 9LpCEP4p53, was found to be more sensitive to cisplatin treatment in vitro than control (9LpCEP4) cells. The in vitro growth rates of control cells and wild-type p53-modified cells were similar in the absence of cisplatin. Fischer 344 rats were implanted intracerebrally with 9LpCEP4p53 cells and intraperitoneally administered 4 mg/kg cisplatin weekly for 7 weeks. These animals survived significantly longer than animals that were implanted with 9LpCEP4p53 cells but were given no cisplatin treatment. In contrast, concurrent cisplatin treatment provided no benefit for animals implanted with 9LpCEP4 cells. Tumors that developed in animals that had been implanted with 9LpCEP4p53 cells and treated with cisplatin had lost expression of wild-type p53, indicating a correlation between expression of wild-type p53 and cisplatin sensitivity in vivo. CONCLUSIONS: The findings of this study suggest that p53-based gene therapy in combination with cisplatin-based chemotherapy may be superior to single-modality treatment in dealing with glioblastoma multiforme.

Animals↗
PubMed2000

[The biosafety of the HSV-TK/GCV gene therapy in five cases of recurrent glioblastoma multiforme].

Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) therapy was performed in five cases of recurrent glioblastoma multiforme. In the last study, the authors demonstrated response of the HSV-TK/GCV therapy against tumor progression (Adachi N, et al.: No Shinkei Geka). The aim of this study is to estimate the biosafety of in vivo HSV-TK gene transfer and GCV administration in five cases. Six parameters were analyzed sequentially up to the 6th month after the vector producer cells (VPCs) inoculation as follows; i) clinical symptom, ii) vital sign, iii) peripheral blood cell count, iv) blood biochemical analysis, v) serological test, vi) molecular biological test in peripheral leukocytes. In addition, ten systemic organs extracted from the two subjects in whom death occurred were also analyzed biologically. One case suffered from transient deterioration of left hemiparesis on the 34th day, which could be considered a probably-related but not adverse event. Serological tests detected anti-VPC antibody at the 1st month in one case and anti-vector antibody at the 1st and 4th month in another. The other examinations revealed no abnormal findings at all. These data indicate that the HSV-TK/GCV therapy might be a satisfactorily safe approach against glioblastoma multiforme.

Adult↗
PubMed2005

Glioblastoma multiforme of the conus medullaris in a child: description of a case and literature review.

We describe a case of glioblastoma multiforme of the conus medullaris in a child. MR imaging showed at the T12-L1 level an intramedullary mass with signal alteration, with only two nodules of contrast enhancement. The finding was consistent with astrocytoma. Pathologic evaluation was consistent with glioblastoma multiforme. Nine months after the surgical treatment, the patient showed leptomeningeal recurrence. This case appears to be unusual for both the hysto-type and the nonspecific MR imaging features.

Adolescent↗
PubMed2006

Intracranial thermotherapy using magnetic nanoparticles combined with external beam radiotherapy: results of a feasibility study on patients with glioblastoma multiforme.

We aimed to evaluate the feasibility and tolerability of the newly developed thermotherapy using magnetic nanoparticles on recurrent glioblastoma multiforme. Fourteen patients received 3-dimensional image guided intratumoral injection of aminosilane coated iron oxide nanoparticles. The patients were then exposed to an alternating magnetic field to induce particle heating. The amount of fluid and the spatial distribution of the depots were planned in advance by means of a specially developed treatment planning software following magnetic resonance imaging (MRI). The actually achieved magnetic fluid distribution was measured by computed tomography (CT), which after matching to pre-operative MRI data enables the calculation of the expected heat distribution within the tumor in dependence of the magnetic field strength. Patients received 4-10 (median: 6) thermotherapy treatments following instillation of 0.1-0.7 ml (median: 0.2) of magnetic fluid per ml tumor volume and single fractions (2 Gy) of a radiotherapy series of 16-70 Gy (median: 30). Thermotherapy using magnetic nanoparticles was tolerated well by all patients with minor or no side effects. Median maximum intratumoral temperatures of 44.6 degrees C (42.4-49.5 degrees C) were measured and signs of local tumor control were observed. In conclusion, deep cranial thermotherapy using magnetic nanoparticles can be safely applied on glioblastoma multiforme patients.

Adult↗
PubMed1987

[Glioblastoma multiforme with extracranial metastases without previous surgery: demonstration of extracranial metastases by peroxidase antiperoxidase staining and clinicopathological study].

Spontaneous extracranial metastases of glioblastoma multiforme in the absence of previous surgery have been rarely reported (Table 1). We presented an autopsy case of glioblastoma multiforme which spontaneously metastasized to the lungs, bronchial lymph nodes, liver, kidney, heart and spleen. A 68-year-old man was admitted to the Department of Neurosurgery at our hospital with chief complaints of right sided weakness in July 1984. He was well until November 1983, when he noticed weakness of right lower extremity followed one month later by the weakness in the right arm. He was treated at another hospital under the diagnosis of cerebral infarction, but his right sided weakness gradually progressed. In June 1984, a diagnosis of brain tumor was made by the neurological findings and CT scan, and he was transferred to our hospital for further evaluation and treatment. Neurological examination revealed disorientation, bilateral papilledema, right hemiparesis, right hyperreflexia and right hemisensory disturbance. CT scan revealed abnormal low density area in the left fronto-parietal lobe (Fig. 1) with irregular enhanced lesions on contrast CT scan (Fig. 2). Chest x-ray showed abnormal shadow in the right middle and lower lobe (Fig. 3) and a diagnosis of pulmonary infarction was suspected. The clinical states of this patient took downhill course and he expired on July 13, 1984 by the complication of disseminated intravascular coagulation syndrome. The brain weight was 1400 gr. Dura mater and falx cerebri were tightly adherent to the left parietal lobe (Fig. 4). Primary brain tumor was found in the left fronto-parietal region. The tumor was poorly defined with necrosis and hemorrhage (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2003

In situ detection of telomeres by fluorescence in situ hybridization and telomerase activity in glioblastoma multiforme: correlation with p53 status, EGFR, c-myc, MIB1, and Topoisomerase IIalpha protein expression.

Aberrations of genes/proteins regulating cell cycle and growth, increased proliferation and telomerase activity (TA) are documentable in glioblastoma multiforme. TA is more frequently detectable in secondary glioblastoma, which is also characterized by p53 mutation/overexpression. Discordant telomere (Te) length values have been reported in glioblastomas with and without TA. In 31 glioblastomas, in which pre-existing astrocytoma was not documented, we compared cases with and without TA for the expression of p53, EGFR, c-Myc, MIB-1 and Topoisomerase IIalpha; p53 mutations were also investigated by SSCP-PCR. Correlations were made with Te parameters [TePs: number (TeNo), length and area] as evaluated by image analysis in interphase nuclei of fluorescence in situ hybridization (FISH)-processed sections. We found no differences in the expression of the proteins evaluated and in TePs, except Te/nuclear area %, which was significantly lower in TA+ cases (p=0.02). TePs were, instead, inversely correlated with TA (p=0.0001). TA was positively correlated with MIB1 staining index in the TA+ cases (p=0.033), which also showed a positive correlation between TeNo and EGFR expression (p=0.042), and a trend towards a negative correlation between TeNo and p53 expression (p=0.05). Tumors overexpressing EGFR had a significantly shorter lifetime (p=0.0001). TeNo seems to be inversely correlated to tumor proliferation and lifetime in glioblastoma multiforme.

Acid Phosphatase↗
PubMed1980

Glioblastoma multiforme with tuberous sclerosis. Report of a case.

Gliomas of the CNS associated with tuberous sclerosis have been well documented; malignant degeneration to glioblastoma multiforme, however, is rare. We studied a 17-year-old boy with stigmata of tuberous sclerosis and a cerebral glioblastoma multiforme. The rarity of this occurrence suggests that neoplasms arising from hamartomas may behave differently than those CNS tumors that arise apparently de novo.

Adolescent↗
PubMed2004

Low-level microsatellite instability phenotype in sporadic glioblastoma multiforme.

PURPOSE: Genetic instability is a hallmark of glioblastoma multiforme (GBM). Microsatellite instability (MSI) is a significant event in the tumorigenesis of many sporadic malignancies. The aim of our investigation was to study microsatellite instability in newly diagnosed glioblastomas. METHODS: MSI was investigated in 109 GBMs with 15 microsatellite markers. Immunohistochemistry was performed for the mismatch repair (MMR) proteins hMLH1, hMSH2, hPMS2, and hMSH6 in cases showing MSI. Sequence and promoter methylation status of hMLH1 were analyzed in the case of a decreased hMLH1 protein expression as well. To further investigate MSI(+) GBMs we carried out studies of LOH at selected chromosome regions, EGFR amplification, and sequence of p53 and PTEN. RESULTS: MSI was observed in six GBMs (5.5%) and it was more frequent in GBMs with a previous lower grade astrocytoma (18.8% vs. 3.2%). MMR protein staining was positive in all MSI(+) GBMs except in one case, which showed an aberrant expression of hMLH1 and hPMS2 without hMLH1 inactivation. Among MSI(+) GBMs, one tumor corresponded to the GBM molecular type 1 (p53 mutation, no EGFR amplification), another tumor to type 2 (wild-type p53, EGFR amplification), and four tumors to neither type (wild-type p53, no EGFR amplification). None of the six tumors carried a PTEN mutation. CONCLUSIONS: MSI in GBM might be caused by inactivation of minor MMR genes rather than by a deficiency of hMLH1 or hMSH2 and it appears not to play a decisive role in the pathogenesis of these tumors. MSI(+) GBMs predominantly showed a profile which included wild-type of p53 and PTEN and absence of EGFR amplification but MSI occurred in all GBM molecular subtypes.

Adolescent↗
PubMed1998

Radiotherapy of glioblastoma multiforme. Feasibility of increased fraction size and shortened overall treatment.

PURPOSE: With regard to the poor prognosis of patients with glioblastoma multiforme, the aspect of life quality with a minimal treatment time becomes essential. The purpose of the present study is to evaluate whether the results of a radiotherapy schedule using increased single fractions applied over a shortened treatment time is feasible without compromising treatment efficiency or providing more side effects than a conventionally fractionated treatment. PATIENTS AND METHODS: A total of 38 patients (f = 21, m = 17, mean age 58 years) with histologically proven glioblastoma multiforme were irradiated after (partial) resection (n = 29) or stereotactic surgery (n = 9) with single doses of 3.5 Gy (ICRU) 5 fractions a week up to a total dose of 42 Gy following individual treatment planning. RESULTS: Median survival was 45.7 weeks, survival rate after 6 months was 80.9% and decreased to 34.2% after 12 months. Radiotherapy was tolerated without any important acute toxicity or any late side effects during the follow-up period. CONCLUSIONS: The increase of the dose per fraction using a fraction size of 3.5 Gy enhanced neither acute nor late toxicity. The survival rate compared well to those described in the literature. Thus the shortened treatment schedule seems as efficient as conventional radiotherapy. Moreover, it seems preferable with regard to quality of life.

Adult↗
PubMed2003

Promising survival for patients with glioblastoma multiforme treated with individualised chemotherapy based on in vitro drug sensitivity testing.

We retrospectively investigated the efficacy and feasibility of individualised chemotherapy based on in vitro drug sensitivity testing (DST) for patients with glioblastoma multiforme. A total of 40 consecutive patients with glioblastoma multiforme (GM) were enrolled into this study between January 1995 and December 2000. The flow cytometric (FCM) detection of apoptosis was used to determine the in vitro sensitivity of tumour cells obtained at surgery to 30 different kinds of anticancer agents. From the results of FCM assay, an in vitro best regimen was prospectively selected. All the patients concurrently received the individualised chemotherapy with the in vitro best regimen and 60 Gy of conventional radiation therapy. Of the 31 assessable patients, eight patients (26%) achieved partial response, and 20 patients (65%) had stable disease. The median survival time was 20.5 months. The individualised chemotherapy based on in vitro DST was associated with favourable survival time for the patients with GM compared with the reported results of conventional therapy regimens. The present result suggests that the currently available anticancer agents could be effective against GM when used in individualised chemotherapy.

Adolescent↗
PubMed1998

Outcome in elderly patients undergoing definitive surgery and radiation therapy for supratentorial glioblastoma multiforme at a tertiary care institution.

PURPOSE: To determine the efficacy of definitive surgery and radiation in patients aged 70 years and older with supratentorial glioblastoma multiforme. METHODS AND MATERIALS: We selected elderly patients (> or = 70 years) who had primary treatment for glioblastoma multiforme at our tertiary care institution from 1977 through 1996. The study group (n = 102) included 58 patients treated with definitive radiation, 19 treated with palliative radiation, and 25 who received no radiation. To compare our results with published findings, we grouped our patients according to the applicable prognostic categories developed by the Radiation Therapy Oncology Group (RTOG): RTOG group IV (n = 6), V (n = 70), and VI (n = 26). Patients were retrospectively assigned to prognostic group IV, V, or VI based on age, performance status, extent of surgery, mental status, neurologic function, and radiation dose. Treatment included surgical resection and radiation (n = 49), biopsy alone (n = 25), and biopsy followed by radiation (n = 28). Patients were also stratified according to whether they were optimally treated (gross total or subtotal resection with postoperative definitive radiation) or suboptimally treated (biopsy, biopsy + radiation, surgery alone, or surgery + palliative radiation). Patients were considered to have a favorable prognosis (n = 39) if they were optimally treated and had a Karnofsky Performance Status (KPS) score of at least 70. RESULTS: The median survival for patients according to RTOG groups IV, V, and VI was 9.2, 6.6, and 3.1 months, respectively (log-rank, p < 0.0004). The median overall survival was 5.3 months. The definitive radiation group (n = 58) had a median survival of 7.3 months compared to 4.5 months in the palliative radiation group (n = 19) and 1.2 months in the biopsy-alone group (p < 0.0001). Optimally treated patients had a median survival of 7.4 months compared to 2.4 months in those suboptimally treated (p < 0.0001). The favorable prognosis group had an 8.4-month median survival compared to 2.4 months in the unfavorable group (p < 0.0001). On multivariate analysis, the KPS, RTOG group, favorable/unfavorable prognosis, and optimal treatment/suboptimal treatment were significant predictors of survival. CONCLUSION: Elderly patients with good performance status (> or = 70 KPS) when treated aggressively with maximal resection and definitive radiation had longer survival than those treated with palliative radiation and biopsy. Aggressive treatment in such patients should be considered.

Aged↗
PubMed1999

The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere.

BACKGROUND: We retrospectively analyzed preoperative and postoperative radiographic tumor volumes in 92 patients who underwent hemispheric glioblastoma multiforme operations (107) to determine the factors that affect time to tumor progression (TTP) and overall survival. METHODS: Quantification of tumor volumes was based on a previously described method involving computerized image analysis of contrast enhancing tumor on computerized tomography or magnetic resonance imaging scans. RESULTS: Among the variables analyzed, preoperative Karnofsky Performance Status (KPS) (p < 0.05), chemotherapy (p < 0.05), percent of resection (POR) (p < 0.001), and volume of residual disease (VRD) (p < 0.001) had a significant effect on TTP. Factors that affected survival were age (p < 0.05), preoperative KPS (p = 0.05), postoperative KPS (p < 0.005), POR (p < 0.0005), and VRD (p < 0.0001). Greater resections did not compromise the quality of life, and patients without any residual disease had a better postoperative KPS than those patients who received less than total resections. CONCLUSIONS: The extent of tumor removal and the amount of residual tumor volume, documented on postoperative imaging studies, are highly significant factors affecting the median time to tumor progression and median survival for patients with glioblastoma multiforme of the cerebral hemisphere.

Adolescent↗
PubMed2004

[Neutron capture therapy in the treatment of glioblastoma multiforme. Initial experience in the Czech Republic].

BACKGROUND: Glioblastoma multiforme is the most frequent primary brain tumor in adults. Despite advances in surgery, radiotherapy and chemotherapy, its treatment remains unsatisfactory with very limited overall survival. In the year 2001, in cooperation with Department of Neurosurgery, Nemocnice Na Homolce and Nuclear Research Institute in Rez, we have started to treat glioblastoma patients with boron neutron capture therapy (BNCT). METHODS AND RESULTS: Cells of malignant brain tumors, especially that of glioblastomas, are able to accumulate boron compounds. If BNCT should be successful, it is necessary to reach selective accumulation of sufficient amount of 10B in the tumor and low accumulation in the normal brain tissue. After BSH administration, radiation with low energy thermal neutrons is delivered. It results in nuclear capture and fission reactions with subsequent selective damage of tumor cells. At the time of analysis 9 patients have been enrolled. Therapy was completed in 5 patients. Treatment has been very well tolerated. We observed minimal acute toxicity associated with radiation and no laboratory abnormalities after administrations of BSH. Unfortunately treatment results were quite unsatisfactory. The median time to progression and overall survival were shorter then expected with conventional treatment. CONCLUSIONS: BNCT is very well tolerated with only a modest toxicity. In contrast to standard radiation, BNCT patients receive only one dose of radiation. Nevertheless, in this small pilot study first results were inferior when compared either to outcomes of conventional therapy or to results reported from other BNCT groups. It might be explained that lower dose of radiation had been used. Further study will show whether the higher dose radiation can improve treatment results.

Adult↗
PubMed1999

Phase II clinical trial of didemnin B in patients with recurrent or refractory anaplastic astrocytoma or glioblastoma multiforme (NSC 325319).

The activity of didemnin B, a natural product derived from the Caribbean Tunic was assessed in 16 patients with Glioblastoma multiforme. Didemnin B was administered intravenously by a short infusion at a dose of 4.3 mg/m2 and subsequently escalated to 6.3 mg/m2. No anti-tumor activity was observed. Toxicity consisted of fatigue, weakness, stomatitis, mild blood count changes, nausea and vomiting and occasional fever. Based on these results further studies with didemnin B in patients with Glioblastoma multiforme are not recommended.

Adult↗
PubMed1995

Expression of p53 in glioblastoma multiforme cells: relationship to survival, proliferation and glycosylation.

Immunohistochemically assessed p53 expression was correlated with overall survival in 20 patients with glioblastoma multiforme. Various epitopes of p53 molecule were detected using DO-1, DO-7, CM-1 and BP-12-53 antibodies, proliferative activity was estimated using anti-PCNA and anti-Ki-67 antibodies and assessment of glycosylation changes using lectin histochemistry completed the study. The results show a statistically significant correlation between DO-1 binding and survival. However, we failed to find any similar statistically significant relationship using other antibodies used in this study. Nor the intensity of proliferative activity show any correlation with either p53 expression or overall survival. Glycosylation in glioblastoma multiforme cells reflected unspecific changes in tumor cells regardless of any relationship to p53 expression. The findings do not provide clear evidence for the predictive value of p53 expression. On the other hand, relatively larger numbers of p53 immunonegative cases may indicate that other mechanisms are involved in the development of this tumor.

Adult↗